POU3F4

POU class 3 homeobox 4, the group of POU class homeoboxes and pseudogenes

Basic information

Region (hg38): X:83508290-83512127

Previous symbols: [ "DFN3" ]

Links

ENSG00000196767 ∙ NCBI:5456 ∙ OMIM:300039 ∙ HGNC:9217 ∙ Uniprot:P49335 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked mixed hearing loss with perilymphatic gusher (Strong), mode of inheritance: XL
• X-linked mixed hearing loss with perilymphatic gusher (Strong), mode of inheritance: XL
• choroideremia-deafness-obesity syndrome (Supportive), mode of inheritance: XL
• mitochondrial non-syndromic sensorineural hearing loss (Supportive), mode of inheritance: Mitochondrial
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, X-linked 2	XL	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial)	Audiologic/Otolaryngologic	5173351; 6662621; 1922747; 7839145; 7581392; 19438930; 19671658; 19930154; 20412083; 21193157; 21250553; 21555964; 23076972; 23606368

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POU3F4 gene.

• X-linked mixed hearing loss with perilymphatic gusher (46 variants)
• not provided (7 variants)
• Rare genetic deafness (3 variants)
• Nonsyndromic genetic hearing loss (1 variants)
• X-linked nonsyndromic hearing loss (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POU3F4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	15	3	22
missense	3	14	31	2	3	53
nonsense	15	3				18
start loss						0
frameshift	36	3				39
inframe indel	1	1	1			3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			4	3		7
Total	55	21	40	20	6

Variants in POU3F4

This is a list of pathogenic ClinVar variants found in the POU3F4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-83508339-C-T			Likely benign (Jun 26, 2023)
X-83508341-C-G		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
X-83508348-C-T		X-linked mixed hearing loss with perilymphatic gusher	Likely benign (Mar 12, 2019)
X-83508383-C-A		not specified	Uncertain significance (May 22, 2019)
X-83508383-C-T			Uncertain significance (Feb 18, 2022)
X-83508386-ACT-A		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (-)
X-83508388-TCTGCGGGCATGCAGCAGGGGAGTCCTTTCCGCAACCCTCAGAAACTTCTCCAAAGTGATTA-T		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)
X-83508402-G-A			Likely benign (Mar 04, 2023)
X-83508403-C-CA		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (-)
X-83508422-AC-A		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)
X-83508423-C-T			Likely benign (May 27, 2022)
X-83508424-C-CCTCA		X-linked mixed hearing loss with perilymphatic gusher	Likely pathogenic (-)
X-83508442-A-AG		X-linked mixed hearing loss with perilymphatic gusher	Likely pathogenic (Apr 27, 2023)
X-83508443-G-C		Inborn genetic diseases	Uncertain significance (Apr 29, 2024)
X-83508450-C-G		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)
X-83508463-C-T		not specified • X-linked mixed hearing loss with perilymphatic gusher • POU3F4-related disorder	Benign/Likely benign (Jan 18, 2024)
X-83508493-TG-T			Pathogenic (Jul 05, 2022)
X-83508494-G-A		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Feb 26, 2019)
X-83508506-T-C			Uncertain significance (Apr 08, 2022)
X-83508515-G-A		X-linked mixed hearing loss with perilymphatic gusher	Likely pathogenic (Jun 05, 2024)
X-83508529-TC-T		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)
X-83508543-CA-C		X-linked mixed hearing loss with perilymphatic gusher	not provided (-)
X-83508545-GC-G		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)
X-83508545-G-GC		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)
X-83508552-GGACCAGCAGGACGT-G		X-linked mixed hearing loss with perilymphatic gusher	Pathogenic (Jan 09, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POU3F4	protein_coding	protein_coding	ENST00000373200	1	1507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.575	0.415	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	83	149	0.556	0.0000107	2350
Missense in Polyphen		17	60.329	0.28179		984
Synonymous	-0.572	75	69.0	1.09	0.00000532	737
Loss of Function	2.07	1	6.83	0.146	4.37e-7	106

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain.

Recessive Scores

• pRec: 0.110

Intolerance Scores

• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.74

Haploinsufficiency Scores

• pHI: 0.783
• hipred: Y
• hipred_score: 0.627
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pou3f4
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;sensory perception of sound;forebrain neuron differentiation;cochlea morphogenesis;negative regulation of mesenchymal cell apoptotic process
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;AT DNA binding;DNA-binding transcription factor activity;protein binding